Some children have visual disturbances that occur in the absence of, or are out of proportion to, their objective ophthalmological findings. These symptoms reflect a wide range of processes that may be benign or a sign of neurological, systemic, or psychiatric disease. This chapter deals with the neuro-ophthalmologic detection of organic and psychogenic disorders that may manifest as transient or unexplained visual loss, along with other episodic visual disturbances that occur in childhood. In these cases, several formidable problems confront the physician who is trying to reach the correct diagnosis. The descriptions of episodic visual disturbances and hallucinations in children are generally less complex in detail than those in the adult population because children have a limited vocabulary and a limited experiential basis of sensory phenomena to draw upon.

Background

Migraine is characterized by headache with symptoms such as intense pain, nausea, vomiting, photophobia, and phonophobia that significantly impact individuals’ lives. The objective of this study was to develop a strategy to measure outcomes from the patients’ perspectives for use in evaluating preventive treatments for migraine.

Methods

This study used a multi-stage process. The first stage included concept identification research through literature review, patient-reported outcome (PRO) instrument content review, and clinician interviews, and resulted in a list of concepts relevant to understand the migraine experience. These results informed the design of the subsequent concept elicitation stage that involved qualitative interviews of adults with migraine to understand their experiences. Information from these two stages was used to develop a conceptual disease model (CDM) of the migraine experience. This CDM was used to identify concepts of interest (COI) to evaluate patient-relevant outcomes for assessing treatment benefit of migraine prophylactics. In the final stage, existing PRO instruments were reviewed to assess coverage of concepts related to the selected COI.

Results

Nine articles from 563 screened abstracts underwent full review to identify migraine-relevant concepts. This concept identification and subsequent concept elicitation interviews (N = 32; 21 episodic migraine; 11 chronic migraine) indicated that people with migraine experience difficulties during and between migraine attacks with considerable day-to-day variability in the impact on movement, ability to perform every day and social activities, and emotion. The CDM organized concepts as proximal to and more distal from disease-defining migraine symptoms, and was used to identify impact on physical function as the key COI. The item level review of PRO instruments revealed that none of the existing PRO instruments were suitable to collect data on impact of migraine on physical functioning, to evaluate treatment benefit.

Conclusions

The impact of migraine includes impairments in functioning during and between migraine attacks that vary considerably on a daily basis. There is a need for novel PRO instruments that reflect patients’ migraine experience to assess treatment benefit of migraine prophylactics. These instruments must evaluate the concepts identified and be able to capture the variability of patients’ experience.

Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Monoclonal antibodies against CGRP (LY2951742, ALD-403, and LBR-101/TEV-48125) or its receptor (AMG334) were subsequently developed. As reviewed in this study, numerous phase 1 and 2 trials and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Being macromolecules, these mAbs are not suitable for oral administration; however, their intravenous or subcutaneous delivery can be performed at relatively low frequency—every month or even quarterly—which enhances patients’ compliance. Although not all migraineurs respond to this treatment, and longer administration periods will be needed to assess long-term effects, the results so far obtained are extraordinarily promising. The future introduction of mAbs on the market will probably represent a turning point for prevention similar to that represented by triptans for abortive treatment in migraine.

Although migraine symptomatology is well-defined, our understanding of migraine pathophysiology is incomplete. Structural and functional brain imaging can contribute to a greater understanding of migraine pathophysiology. Recent neuroimaging studies demonstrate that migraine is associated with structural and functional alterations of brain regions commonly implicated in pain processing. This review summarizes recent brain structural and functional imaging findings in migraine and highlights those that are associated with characteristics such as the presence or absence of aura, associated cognitive dysfunction, sex-differences (male vs. female migraineurs), age, and disease burden.

Background

Reports have suggested that abnormal cortical excitability may be associated with acute migraines. The present study quantitatively assesses the degree of cortical excitability in chronic migraine as compared to acute migraine and healthy controls within the pediatric population.

Methods

We investigated 27 children suffering from chronic migraine, 27 children suffering from acute migraine, and 27 healthy controls using a magnetoencephalography (MEG) system, recording at a sampling rate of 6000 Hz. All groups were age-matched and gender-matched. Neuromagnetic brain activation was elicited by a finger-tapping motor task. The spatiotemporal and spectral signatures of MEG data within a 5–2884 Hz range were analyzed using Morlet wavelet transform and beamformer analyses.

Results

Compared with controls, the chronic migraine group showed (1) significantly prolonged latencies of movement-elicited magnetic fields (MEFs) between 5 and 100 Hz; (2) increased spectral power between 100 and 200 Hz, and between 2200 and 2800 Hz; and (3) a higher likelihood of neuromagnetic activation in the ipsilateral sensorimotor cortices, supplementary motor area, and occipital regions. Compared with acute migraine group, chronic migraine patients showed (1) significantly higher odds of having strong MEFs after 150 ms; and (2) significantly higher odds of having neuromagnetic activation from the deep brain areas.

Conclusions

Results demonstrated that chronic migraine subjects were not only different from the healthy controls, but also different from acute migraine subjects. The chronification of migraines may be associated with elevated cortical excitability, delayed and spread neural response, as well as aberrant activation from deep brain areas.

Classification has played a major role in the diagnosis of primary headache conditions including migraine with and without aura. With many updates and changes, the International Classification of Headache Disorders (ICHD)-3 beta is currently considered as the gold standard for classification of migraine and other headaches. Correct diagnosis of migraine and its subtypes is a first step toward appropriate treatment and crucial to minimizing disability and optimizing health-related quality of life. The ICHD-3 beta version represents the state of the art in migraine diagnosis but is expected to evolve as biological knowledge advances. Future research should focus on identification of biologically homogeneous subgroups of migraine based on genes and biomarkers.

Opinion statement

While the diagnosis of migraine in children is generally straightforward, treatment can seem complex with a number of medication choices, many of which are used “off label.” Patients with intermittent migraines can often be managed with ibuprofen or naproxen taken as needed. Unfortunately, by the time that children present to our practice, they have often tried these medications without improvement. Triptans are frequently prescribed to these patients with good success. It is important to make the patient aware of the possible associated serotonergic reactions. If the patient is having more than one headache per week or the headaches are prolonged, prophylactic treatment is indicated. In our practice, the overwhelming majority of these patients will be treated with amitriptyline or topiramate. We generally allow side effect tolerability to guide our choice of medication. Cyproheptadine is often used in younger patients as it comes in a liquid form. There is evidence supporting the use of propranolol, though the potential worsening of underlying asthma symptoms may limit its use, and sodium valproate, which must be used with caution in female patients of childbearing age due to significant teratogenicity risks. Other prophylactic treatments with less robust evidence include the antiepileptic drugs gabapentin, zonisamide, and levetiracetam; calcium channel blockers such as verapamil and amlodipine; and the angiotensin receptor blocking agent candasartin (not available in the USA). Almost all patients in our practice are advised to take magnesium supplementation. Magnesium is a supplement with relatively few adverse effects and good evidence for improvement of migraine symptoms. We evaluate lifestyle issues and comorbidities in all our patients. Ignoring these will make successful treatment near impossible. Good sleep, adequate hydration, appropriate diet, and exercise are vitally important. Finally, most of our patients benefit from a psychology evaluation with cognitive behavioral therapy. Stress management and biofeedback are tremendously helpful in improving quality of life in migraineurs.

While over half of women with migraine report improvement during pregnancy, having a history of migraine may increase the chance of negative health outcomes. The state of pregnancy increases the risk of several dangerous secondary headache disorders, especially those associated with hypertensive disorders of pregnancy, and providers need to know the red flags to diagnose and treat emergently. Non-pharmacological migraine treatments can be instituted in advance of pregnancy as many are considered the safest options during pregnancy, but understanding the safety of medications and dietary supplements ensures appropriate care for the refractory migraine patient. New controversy exists over the safety of several historically routine and safe migraine treatment options in pregnancy, such as magnesium, acetaminophen, ondansetron, and butalbital. While it is not clear if breastfeeding decreases the postpartum recurrence of migraine, understanding safe treatment options during lactation can allow women to continue breastfeeding while achieving migraine relief.

Background

Migraine is characterized by a series of phases (inter-ictal, pre-ictal, ictal, and post-ictal). It is of great interest whether resting-state electroencephalography (EEG) is differentiable between these phases.

Methods

We compared resting-state EEG energy intensity and effective connectivity in different migraine phases using EEG power and coherence analyses in patients with migraine without aura as compared with healthy controls (HCs). EEG power and isolated effective coherence of delta (1–3.5 Hz), theta (4–7.5 Hz), alpha (8–12.5 Hz), and beta (13–30 Hz) bands were calculated in the frontal, central, temporal, parietal, and occipital regions.

Results

Fifty patients with episodic migraine (1–5 headache days/month) and 20 HCs completed the study. Patients were classified into inter-ictal, pre-ictal, ictal, and post-ictal phases (n = 22, 12, 8, 8, respectively), using 36-h criteria. Compared to HCs, inter-ictal and ictal patients, but not pre- or post-ictal patients, had lower EEG power and coherence, except for a higher effective connectivity in fronto-occipital network in inter-ictal patients (p < .05). Compared to data obtained from the inter-ictal group, EEG power and coherence were increased in the pre-ictal group, with the exception of a lower effective connectivity in fronto-occipital network (p < .05). Inter-ictal and ictal patients had decreased EEG power and coherence relative to HCs, which were “normalized” in the pre-ictal or post-ictal groups.

Conclusion

Resting-state EEG power density and effective connectivity differ between migraine phases and provide an insight into the complex neurophysiology of migraine.

Migraine and obesity are each prevalent disorders involving significant personal and societal burden. Epidemiologic research demonstrates a link between migraine and obesity that is further substantiated by putative behavioral, psychosocial, and physiological mechanisms. As obesity is considered a modifiable risk factor for exacerbation of migraine, weight loss may be a particularly useful treatment option for people with comorbid migraine and obesity. Behavioral weight loss interventions complement existing behavioral treatments for migraine and offer patients evidence-based effective strategies for achieving weight loss that could help reduce frequency, severity, and impact of migraine attacks.